The Challenging\nConformational Landscape of Cysteamine···H<sub>2</sub>O Revealed by the Strong Interplay of Rotational Spectroscopy\nand Quantum Chemical Calculations

A 1:1 molecular complex of cysteamine with water is shown\nto adopt\na cage-like structure where cysteamine accepts a relatively strong\nhydrogen bond from water while also engaging in two additional weaker\ninteractions (SH···O<sub>w</sub> and CH···O<sub>w</sub>). Experimental and theoretical approaches confirm this conformer\nas the global minimum on the potential energy surface. Fitting of\nkey structural parameters to experimentally determined moments of\ninertia yields consistent and accurate results for rotational and <sup>14</sup>N nuclear quadrupole coupling constants which are shown to\nbe challenging to calculate using <i>ab initio</i> methods.\nComprehensive analysis of the intermolecular interactions and a thorough\ncomparison with the properties of aminoethanol–water is presented,\nutilizing independent gradient models based on Hirshfeld partition,\nquantum theory of atoms-in-molecules, and symmetry-adapted perturbation\ntheory approaches. As expected, the OH group of aminoethanol is a\nstronger hydrogen bond donor than the SH group in cysteamine, while\nthe CH···O<sub>w</sub> interaction is a key determining\nfactor of the conformational landscape in both cysteamine–water\nand aminoethanol–water complexes. The results show very clearly\nthat the synergy between theoretical calculations and experimental\nresults is not only desirable but mandatory to get the right answers\nin such complex conformational surfaces. The results are also clear\nbenchmarks for the accuracy of different theoretical methods in assessing\nthe structures and energy order of the conformations.